Evidence map›Paper›PMID 34242585›Full record

ArticleDevelopmental cell2021

A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies.

Gerald C Tiu, Craig H Kerr, Craig M Forester, Pallavi S Krishnarao, Hannah D Rosenblatt, Nitin Raj, Travis C Lantz, Olena Zhulyn, Margot E Bowen, Leila Shokat and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 53 citations in OpenAlex.

  1. Trial
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  10. HemaSphere · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Gerald C TiuDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Stanford Medical Scientist Training Program, Stanford University, Stanford, CA 94305, USA.
Craig H KerrDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Craig M ForesterHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Division of Pediatric Allergy, Immunology and Bone Marrow Transplantation, University of California, San Francisco, San Francisco, CA 94143, USA; Children's Hospital Colorado, Division of Pediatric Hematology/Oncology/Bone Marrow Transplant, Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Pallavi S KrishnaraoDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Hannah D RosenblattDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Nitin RajDivision of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Travis C LantzDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Olena ZhulynDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Margot E BowenDivision of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Leila ShokatDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Laura D AttardiDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Davide RuggeroDepartment of Urology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: davide.ruggero@ucsf.edu.
Maria BarnaDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: mbarna@stanford.edu.
Stanford University · USUCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of Colorado Anschutz Medical Campus · US

Funding

GENETICS TRAINING PROGRAM FOR PHD CANDIDATEST32GM007790 · NIGMS · STANFORD UNIVERSITY · PI BRUNET, ANNE, KINGSLEY, DAVID M · 1985 to 2020
$12.8M
Integrative approaches to elucidate p53 transcriptional networks during carcinogenesisR35CA197591 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI · 2015 to 2026
$11.6M
Mechanisms of regulated translation control in cancer and its therapeutic implicationsR35CA242986 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUGGERO, DAVIDE · 2019 to 2025
$6.4M
Research Training in Childhood CancerT32CA128583 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Eric Alejandro Sweet-Cordero · 2007 to 2026
$6.0M
Specialized Translational Control of Stem Cell Differentiation and Embryonic DevelopmentR01HD086634 · NICHD · STANFORD UNIVERSITY · PI BARNA, MARIA · 2016 to 2025
$5.5M
Child Health Career Development Program at UCSFK12HD072222 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIERO, DONNA M. · 2013 to 2017
$2.0M
Profiling Translational Control of Gene Expression and Nascent Proteomic Responses in Erythropoietic Progression and RibosomopathiesK08DK119561 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI FORESTER, CRAIG M. · 2019 to 2022
$781k
NCI NIH HHS R35 CA197591NCI NIH HHS R35 CA242986NCI NIH HHS T32 CA128583NICHD NIH HHS K12 HD072222NICHD NIH HHS R01 HD086634NIDDK NIH HHS K08 DK119561NIGMS NIH HHS T32 GM007790
6 · The paper itself

Abstract

In ribosomopathies, perturbed expression of ribosome components leads to tissue-specific phenotypes. What accounts for such tissue-selective manifestations as a result of mutations in the ribosome, a ubiquitous cellular machine, has remained a mystery. Combining mouse genetics and in vivo ribosome profiling, we observe limb-patterning phenotypes in ribosomal protein (RP) haploinsufficient embryos, and we uncover selective translational changes of transcripts that controlling limb development. Surprisingly, both loss of p53, which is activated by RP haploinsufficiency, and augmented protein synthesis rescue these phenotypes. These findings are explained by the finding that p53 functions as a master regulator of protein synthesis, at least in part, through transcriptional activation of 4E-BP1. 4E-BP1, a key translational regulator, in turn, facilitates selective changes in the translatome downstream of p53, and this thereby explains how RP haploinsufficiency may elicit specificity to gene expression. These results provide an integrative model to help understand how in vivo tissue-specific phenotypes emerge in ribosomopathies.

Indexed as

HaploinsufficiencyProtein BiosynthesisProtein Processing, Post-TranslationalAdaptor Proteins, Signal TransducingAnimalsBody PatterningCell Cycle ProteinsExtremitiesGene Expression Regulation, DevelopmentalMiceMice, KnockoutPhenotypeRibosomal ProteinsRibosomesTumor Suppressor Protein p53Adaptor Proteins, Signal TransducingCell Cycle ProteinsEif4ebp1 protein, mouseRibosomal ProteinsTrp53 protein, mouseTumor Suppressor Protein p534E-BP1limb developmentnucleolar stressp53ribosomal protein haploinsufficiencyribosome profilingribosomopathytranslational control

Identifiers

PMID34242585
PMCPMC8319123
OpenAlexW3182281978

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.